Dr. Forester aims to become an independent investigator in the field of geriatric bipolar disorder using magnetic resonance spectroscopy (MRS) to study biochemical markers of treatment response. Long-term career goals include collaboration with other centers employing MR imaging (MRI) technologies to study geriatric bipolar disorder with a focus on developing safe and effective therapeutic interventions. Dr. Forester will be mentored at McLean Hospital by Dr. Bruce Cohen, past President of McLean Hospital and current Director of the Frazier Institute, an interdisciplinary consortium studying bipolar disorder using clinical pharmacology, MRS, functional MR and laboratory techniques, and co-mentored by Dr. Perry Renshaw, of the McLean Hospital Brain Imaging Center. Dr. Forester will enhance his clinical skills with formal training in MRI techniques and applications, biostatistics and the responsible conduct of research. The proposed research plan will employ MRS to study measures of brain energy metabolism in 35 older adults with bipolar depression and 25 healthy age-matched controls. Subjects meeting inclusion criteria will be clinically characterized at baseline with a structured psychiatric interview and neuropsychological testing and will undergo proton (1H) MRS study at 4 Tesla. Subjects with bipolar depression will then receive open label treatment with lamotrigine as monotherapy or adjunctive therapy for eight weeks. At the end of 8 weeks, both groups will undergo a second 1H MRS scan at 4 Tesla. Group differences in the brain energy metabolites, glutamate, glutamine, N-acetyl aspartate and lactate, among control subjects and subjects with bipolar disorder will be analyzed at baseline and after treatment. PUBLIC HEALTH RELEVANCE: Bipolar disorder is a significant health care issue for elderly individuals, which is associated with disability, functional decline, mortality and increased demands on the public health system. The treatment of bipolar depression in later life is complex and challenging, with little systematic research available to guide therapeutic interventions. This study will examine biochemicals associated with brain energy metabolism before and after treatment with a mood stabilizing medication. Information from this and future related studies of geriatric bipolar depression might help inform the development of more effective and safe treatments.